A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Status and phase

Completed

Phase 1

Conditions

Cancer, Advanced Solid Tumors

Treatments

Drug: ARQ 197

Study type

Interventional

Funder types

Industry

Identifiers

NCT00612209

ARQ 197-103

Details and patient eligibility

About

This is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors.

Full description

Patients will take ARQ 197 orally twice daily continuously at dose levels specified for their respective dose cohorts. The ARQ 197 starting dose will be a total daily dose of 200 mg (100 mg bid). ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is designed as four weeks (28 days) and will be repeated without therapy interruption.

Enrollment

51 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed written informed consent must be obtained and documented according to ICH GCP, the local regulatory requirements, and permission to use private health information in accordance with HIPPA prior to study-specific screening procedures
A histologically or cytologically confirmed advanced solid tumor, including 10 patients with advanced prostate cancers in the expansion cohort.
≥ 18 years of age.
Patients must have accessible tumor that is safely amenable to tumor biopsies.
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
Tumor imageable by DCE-MRI preferably > 3cm in abdomen, pelvis, head/neck or peripheral limb (only for 12 patients undergoing MRI studies including DCE-MRI and DW-MRI in the expanded cohort)
Karnofsky performance status (KPS) ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last ARQ 197 dose
Females of childbearing potential must have a negative serum pregnancy test
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0 × ULN with metastatic liver disease
Hemoglobin ≥ 10 g/dl
Total bilirubin ≤ 1.5 × ULN
Creatinine ≤ 1.5 x ULN
Absolute neutrophil count ≥ 1.5 x 10^9/L
Platelets ≥ 100 x 10^9/L

The following inclusion criteria apply to patients with prostate cancer only:

Histologically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following castration
PSA or radiological evidence for progressive prostate cancer
Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy before and during the trial.
Castrate testosterone level [< 50 ng/dL or < 2.00 nmol/L (nmol/L x 28.8 = ng/dL)]

Exclusion criteria

Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks prior to first dose of ARQ 197
Surgery within 4 weeks prior to first dose
Known untreated brain metastases
Pregnant or breastfeeding
Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
Unable or unwilling to swallow ARQ 197 capsules twice daily
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
For patients undergoing magnetic resonance imaging (MRI) studies (including DCE-MRI and DW-MRI) in the expanded cohort:
Contraindications to MRI, e.g. contraindicated metal implants
Patients with Creatinine > x1 ULN
Patients without antecubital fossa venous access